title: Mice with a mutation in the dynein heavy chain 1 gene display sensory neuropathy but lack motor neuron disease.
abstract: In neurons, cytoplasmic dynein functions as a molecular motor responsible for retrograde axonal transport. An impairment of axonal transport is thought to play a key role in the pathogenesis of neurodegenerative diseases such as amyotrophic lateral sclerosis, the most frequent motor neuron disease in the elderly. In this regard, previous studies described two heterozygous mouse strains bearing missense point mutations in the dynein heavy chain 1 gene that were reported to display late-onset progressive motor neuron degeneration. Here we show, however, that one of these mutant strains, the so-called Cra mice does not suffer from motor neuron loss, even in aged animals. Consistently, we did not observe electrophysiological or biochemical signs of muscle denervation, indicative of motor neuron disease. The "hindlimb clasping" phenotype of Cra mice could rather be due to the prominent degeneration of sensory neurons associated with a loss of muscle spindles. Altogether, these findings show that dynein heavy chain mutation triggers sensory neuropathy rather than motor neuron disease.
authors.affiliation: INSERM, U692, Laboratoire de Signalisations Moléculaires et Neurodégénérescence, Strasbourg, F-67085, France. ldupuis@neurochem.u-strasbg.fr
authors.forename: Luc
authors.initials: L
authors.lastname: Dupuis
authors.forename: Anissa
authors.initials: A
authors.lastname: Fergani
authors.forename: Kerstin E
authors.initials: KE
authors.lastname: Braunstein
authors.forename: Judith
authors.initials: J
authors.lastname: Eschbach
authors.forename: Nathalie
authors.initials: N
authors.lastname: Holl
authors.forename: Frédérique
authors.initials: F
authors.lastname: Rene
authors.forename: Jose-Luis
authors.initials: JL
authors.lastname: Gonzalez De Aguilar
authors.forename: Björn
authors.initials: B
authors.lastname: Zoerner
authors.forename: Birgit
authors.initials: B
authors.lastname: Schwalenstocker
authors.forename: Albert C
authors.initials: AC
authors.lastname: Ludolph
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Loeffler
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D001572:Benzofurans; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D056445:Cytoplasmic Dyneins; D004195:Disease Models, Animal; D004398:Dyneins / Q000235:genetics*; D004576:Electromyography / Q000379:methods; D051379:Mice; D008809:Mice, Inbred C3H; D008817:Mice, Mutant Strains; D016472:Motor Neuron Disease / Q000235:genetics / Q000503:physiopathology; D009046:Motor Neurons / Q000473:pathology; D009121:Muscle Denervation / Q000379:methods; D018482:Muscle, Skeletal / Q000502:physiology; D009154:Mutation / Q000235:genetics*; D009469:Neuromuscular Junction / Q000473:pathology; D012678:Sensation Disorders / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D013126:Spinal Nerve Roots / Q000473:pathology; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1
chemical_list: D001572:Benzofurans; C516947:Dync1h1 protein, mouse; C038675:true blue; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D002795:Choline O-Acetyltransferase; D056445:Cytoplasmic Dyneins; D004398:Dyneins